Cytogenetic changes and malignancy. We shall continue to explore the role of specific cytogenetic changes in murine and human lymphomas and leukemias, with particular focus on the occurrence and physiological role of chromosome 15 trisomy in the murine T-lymphoma and/or the 8:14 translocation in the human B lymphoma system. Somatic hybridization in vitro. Continued studies will focus on the expression of surface markers, including genetically determined, differentiation related, virally induced and tumor associated markers. The information on the tumor associated markers may be helpful for a more rational design of "xenogenization experiments". For the EBV-system, the hybrid studies may decisively answer the important question whether the specific chromosomal change or the viral genome are essential for the maintenance of in vivo tumorigenicity. Continued studies of host-tumor cell fusion in vivo. We shall explore the kinetics of in vivo fusion, and perform marker studies that may be helpful in deciding which host cell types are involved. We shall try to utilize the system for the in vivo production of hybridomas and T/T cell hybrids. As a further step in our analysis of malignancy by somatic hybridization, we shall test the tumorigenicity of tumor-host cell hybrids that were generated after short term in less than 24 hours after inoculation. Development of new variant and mutant lines. By the use of our recently developed column selection method we shall generate immunoresistant sublines with reduced antigenicity and an increased ability to survive in face of host rejection. This approach also permits a study of the question whether the serologically defined, i.e. antibody binding surface sites are identical with the targets of cell mediated rejection. Genetic control of the immune response. This study focuses on the dissection of F1 hybrid resistance patterns against different tumors. We shall analyse the H-2 linked localization of resistance, in relation to the linkage relationships already demonstrated. We shall also explore the suggested connection between in vivo hybrid resistance and in vitro natural killer (NK) cell activity.